Ferroportin1 is required for normal iron cycling in zebrafish

Paula G. Fraenkel, David Traver, Adriana Donovan, David Zahrieh, Leonard I. Zon

Research output: Contribution to journalArticle

67 Citations (Scopus)

Abstract

Missense mutations in ferroportin1 (fpn1), an intestinal and macrophage iron exporter, have been identified between transmembrane helices 3 and 4 in the zebrafish anemia mutant weissherbst (wehTp85c-/-) and in patients with type 4 hemochromatosis. To explore the effects of fpn1 mutation on blood development and iron homeostasis in the adult zebrafish, wehTp85c-/- zebrafish were rescued by injection with iron dextran and studied in comparison with injected and uninjected WT zebrafish and heterozygotes. Although iron deposition was observed in all iron-injected fish, only wehTp85c-/- zebrafish exhibited iron accumulation in the intestinal epithelium compatible with a block in iron export. Iron injections initially reversed the anemia. However, 8 months after iron injections were discontinued, weh Tp85c-/- zebrafish developed hypochromic anemia and impaired erythroid maturation despite the persistence of iron-loaded macrophages and elevated hepatic nonheme iron stores. Quantitative real-time RT-PCR revealed a significant decrease in mean hepatic transcript levels of the secreted iron-regulator hepcidin and increased intestinal expression of fpn1 in anemic wehTp85c-/- adults. Injection of iron dextran into WT or mutant zebrafish embryos, however, resulted in significant increases in hepcidin expression 18 hours after injection, demonstrating that hepcidin expression in zebrafish is iron responsive and independent of fpn1's function as an iron exporter.

Original languageEnglish (US)
Pages (from-to)1532-1541
Number of pages10
JournalJournal of Clinical Investigation
Volume115
Issue number6
DOIs
StatePublished - Jun 1 2005
Externally publishedYes

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Zebrafish
Iron
Hepcidins
Injections
Dextrans
Anemia
Macrophages
Hypochromic Anemia
Liver
Missense Mutation
Intestinal Mucosa
Heterozygote
Real-Time Polymerase Chain Reaction
Fishes
Homeostasis

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Ferroportin1 is required for normal iron cycling in zebrafish. / Fraenkel, Paula G.; Traver, David; Donovan, Adriana; Zahrieh, David; Zon, Leonard I.

In: Journal of Clinical Investigation, Vol. 115, No. 6, 01.06.2005, p. 1532-1541.

Research output: Contribution to journalArticle

Fraenkel, Paula G. ; Traver, David ; Donovan, Adriana ; Zahrieh, David ; Zon, Leonard I. / Ferroportin1 is required for normal iron cycling in zebrafish. In: Journal of Clinical Investigation. 2005 ; Vol. 115, No. 6. pp. 1532-1541.
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